Factors influencing routine cognitive impairment screening in older at-risk drinkers: Findings from a qualitative study in the United Kingdom

Cognitive Impairment (CI) screening is recommended for those engaged in harmful levels of alcohol use. However, there is a lack of evidence on implementation. This paper explores the barriers and facilitators to CI screening experienced across a service specifically for older drinkers. The findings draw on data gathered as part of an evaluation of a multilevel programme to reduce alcohol-related harm in adults aged 50 and over in five demonstration areas across the United Kingdom. It is based on qualitative interviews and focus groups with 14 service providers and 22 service users. Findings are presented thematically under the section headings: acceptability of screening, interpretation and making sense of screening and treatment options. It is suggested that engagement with CI screening is most likely when its fit with agency culture and its purpose is clear; where service providers have the technical skills to administer and discuss the results of screening with service users; and where those undertaking screening have had the opportunity to reflect on their own experience of being screened. Engagement with CI screening is also most likely where specific intervention pathways and engagement practices can be accessed to respond to assessed need.     

Pharmacokinetics and pharmacodynamics of prolonged oral etoposide in women with metastatic breast cancer

The pharmacokinetics and pharmacodynamics of prolonged oral etoposide chemotherapy were investigated in 15 women with metastatic breast cancer who received oral etoposide 100 mg as a single daily dose for up to 15 days. There was considerable interpatient variability in the day 1 pharmacokinetic parameters: area under the plasma concentration time curve (AUC) (0–24 h) 1.95±0.87 mg/ml per min (mean ± SD), apparent oral clearance 60.9±21.7 ml/min per 1.73 m², peak plasma concentration 5.6±2.5 g/ml, time to peak concentration 73±35 min and half-life 220±83 min. However, intrapatient variability in systemic exposure to etoposide was much less with repeated doses. The intrapatient coefficient of variation (CV) of AUC for day 8 relative to day 1 was 20% and for day 15 relative to day 1 was 15%, compared to the day 1 interpatient CV of 45%. Neutropenia was the principal toxicity. Day 1 pharmacokinetic parameters were related to the percentage decrease in absolute neutrophil count using the sigmoidal E_max equation. A good fit was found between day 1 AUC and neutrophil toxicity (R ²=0.77). All patients who had a day 1 AUC>2.0 mg/ml per min had WHO grade III or IV neutropenia. The predictive performance of the models for neutrophil toxicity was better for AUC (percentage mean predictive error 5%, percentage root mean square error 18.1%) than apparent oral clearance, peak plasma concentration, or daily dose (mg/m²). A limited sampling strategy was developed to predict AUC using a linear regression model incorporating a patient effect. Data sets were divided into training and test sets. The AUC could be estimated using a model utilizing plasma etoposide concentration at only two time points, 4 h and 6 h after oral dosing (R ²=98.9%). The equation AUC_pr=–0.376+0.631×C_4h+0.336×C_6h was validated on the test set with a relative mean predictive error of –0.88% and relative root mean square error of 6.4%. These results suggest monitoring of AUC to predict subsequent myelosuppression as a strategy for future trials with oral etoposide.Division of Haematology and Medical Oncology, Peter MacCallum Cancer Institute, Locked Bag 1, A'Beckett St, Melbourne 3000, Australia     

Developing rational protocols for paediatric psychopharmacological prescribing.

The number of child psychiatrists, paediatricians and general practitioners prescribing psychotropic medication for children in the UK is increasing. Medication is being used not just to treat children of normal intelligence with hyperkinetic disorder or depression, but also to modify behavioural problems in children with developmental disorders and severe learning difficulties. Literature reviews highlight the lack of robust randomized controlled drug trials on which to base clinical practice and the authors have found no appropriate existing protocols to help develop a systematized approach. Against such a background the authors have developed a comprehensive set of protocols covering prescribing details for individual drugs, and also addressing issues such as informed consent, long-term monitoring and school liaison. All children referred to the authors' clinics go through a standardized decision-making process. This article describes both the protocols themselves and the philosophies that guided their development. The authors describe how such a system benefits the children, their families, general practitioners and schools, whilst also facilitating audit and research.     

Paradoxical vocal cord motion causing stridor after thyroidectomy

Two women developed stridor immediately after thyroidectomy as a result of paradoxical vocal cord motion. In both cases the cord function showed a normal pattern during vocalisation but paradoxical movement was seen at laryngoscopy during tidal breathing. The abnormality improved in both patients over time with speech therapy. Whilst the syndrome of paradoxical vocal cord motion is classically thought to have a largely psychological aetiology, subtle interference with laryngeal innervation at surgery is more likely to have been the cause in these cases.     

AUTOPSY FINDINGS IN THE WOLCOTT-RALLISON SYNDROME

Wolcott-Rallison syndrome is a rare autosomal recessive condition characterized by diabetes mellitus arising in early infancy and multiple epiphyseal dysplasia. To date, nine cases have been described in the world literature. We report an affected girl who died at the age of 4 years and on whom a full autopsy was performed. In addition to neonatal diabetes mellitus and epiphyseal dysplasia, this child had mental retardation and recurrent episodes of self-limiting hepatic failure. Autopsy revealed severe pancreatic hypoplasia and markedly abnormal pancreatic histology, while histology of the bone was consistent with epiphyseal dysplasia. There was laryngeal stenosis and pulmonary hypoplasia. The heart was enlarged with mitral valve dysplasia and stenosis, left atrial dilatation, left ventricular hypertrophy, and endocardial fibroelastosis. Examination of the central nervous system showed arrhinencephaly and cerebellar cortical dysplasia. The liver showed minor histological abnormalities but no features were present to account for the recurrent hepatic failure. In addition to Wolcott-Rallison syndrome this child had a deletion at 15q11-12 in 65 of her cells.     

A longitudinal study of maternal bloodflow in normal pregnancy and the puerperium: analysis of Doppler waveforms using Laplace transform techniques

Objective To describe changes in the maternal cerebral circulation and the external iliac arteries throughout pregnancy and the puerperium using the Laplace transform analysis of Doppler waveforms.
Design A prospective longitudinal study.
Setting Department of Obstetrics and Gynaecology, Nottingham University Hospital.
Sample A cohort of 17 healthy women studied every four weeks from early pregnancy until term and up to three months postpartum. Pre-conception data were available for 10 subjects.
Methods Doppler signals were recorded from the internal carotid, middle cerebral and external iliac arteries. The waveforms were analysed using two different techniques: standard indices (systolic: diastolic ratio, pulsatility and resistance indices) and Laplace transform analysis, an alternative method of waveform shape analysis which may provide additional haemodynamic information.
Results Vessel wall tone decreased at an early stage in pregnancy in the cerebral circulation and in the external iliac artery, but this rose again following delivery. The Laplace transform analysis techniques suggest dramatic eight-fold increases in downstream resistance within the external iliac artery in the second half of pregnancy. An increase in downstream resistance to flow also occurred in the internal carotid artery whereas more stable conditions were noted in the middle cerebral artery.
Conclusions Having a preliminary idea of the normal ranges for the Laplace transform analysis variables during pregnancy in a variety of maternal vessels, haemodynamic changes in pregnancies complicated by conditions, such as pre-eclampsia, can now be studied.